Photobiomodulation inside the brain: a novel method of applying near-infrared light intracranially and its impact on dopaminergic cell survival in MPTP-treated mice.

OBJECT: Previous experimental studies have documented the neuroprotection of damaged or diseased cells after applying, from outside the brain, near-infrared light (NIr) to the brain by using external light-emitting diodes (LEDs) or laser devices. In the present study, the authors describe an effective and reliable surgical method of applying to the brain, from inside the brain, NIr to the brain. They developed a novel internal surgical device that delivers the NIr to brain regions very close to target damaged or diseased cells. They suggest that this device will be useful in applying NIr within the large human brain, particularly if the target cells have a very deep location. METHODS: An optical fiber linked to an LED or laser device was surgically implanted into the lateral ventricle of BALB/c mice or Sprague-Dawley rats. The authors explored the feasibility of the internal device, measured the NIr signal through living tissue, looked for evidence of toxicity at doses higher than those required for neuroprotection, and confirmed the neuroprotective effect of NIr on dopaminergic cells in the substantia nigra pars compacta (SNc) in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson disease in mice. RESULTS: The device was stable in freely moving animals, and the NIr filled the cranial cavity. Measurements showed that the NIr intensity declined as distance from the source increased across the brain (65% per mm) but was detectable up to 10 mm away. At neuroprotective (0.16 mW) and much higher (67 mW) intensities, the NIr caused no observable behavioral deficits, nor was there evidence of tissue necrosis at the fiber tip, where radiation was most intense. Finally, the intracranially delivered NIr protected SNc cells against MPTP insult; there were consistently more dopaminergic cells in MPTP-treated mice irradiated with NIr than in those that were not irradiated. CONCLUSIONS: In summary, the authors showed that NIr can be applied intracranially, does not have toxic side effects, and is neuroprotective.

BioMEA: a versatile high-density 3D microelectrode array system using integrated electronics.

Microelectrode arrays (MEAs) offer a powerful tool to both record activity and deliver electrical microstimulations to neural networks either in vitro or in vivo. Microelectronics microfabrication technologies now allow building high-density MEAs containing several hundreds of microelectrodes. However, dense arrays of 3D micro-needle electrodes, providing closer contact with the neural tissue than planar electrodes, are not achievable using conventional isotropic etching processes. Moreover, increasing the number of electrodes using conventional electronics is difficult to achieve into compact devices addressing all channels independently for simultaneous recording and stimulation. Here, we present a full modular and versatile 256-channel MEA system based on integrated electronics. First, transparent high-density arrays of 3D-shaped microelectrodes were realized by deep reactive ion etching techniques of a silicon substrate reported on glass. This approach allowed achieving high electrode aspect ratios, and different shapes of tip electrodes. Next, we developed a dedicated analog 64-channel Application Specific Integrated Circuit (ASIC) including one amplification stage and one current generator per channel, and analog output multiplexing. A full modular system, called BIOMEA, has been designed, allowing connecting different types of MEAs (64, 128, or 256 electrodes) to different numbers of ASICs for simultaneous recording and/or stimulation on all channels. Finally, this system has been validated experimentally by recording and electrically eliciting low-amplitude spontaneous rhythmic activity (both LFPs and spikes) in the developing mouse CNS. The availability of high-density MEA systems with integrated electronics will offer new possibilities for both in vitro and in vivo studies of large neural networks.